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Biomedical subjects

J Osterloh

Publications and source records attributed to J Osterloh.

At least 19 recordsLinked to original sources
PubMed2005

Factors influencing the difference between maternal and cord blood lead.

AIMS: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. METHODS: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. RESULTS: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. CONCLUSION: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

Adult↗
PubMed2002

Synthesis, dark toxicity and induction of in vitro DNA photodamage by a tetra(4-nido-carboranylphenyl)porphyrin.

The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.

Animals↗
PubMed2000

Patterns and determinants of blood lead during pregnancy.

The pattern of blood lead during pregnancy was investigated in a cohort of 195 women who, between October 1992 and February 1995, entered prenatal care at Magee-Womens Hospital in Pittsburgh, Pennsylvania, by week 13 of pregnancy. Blood was drawn as many as five times, once in each of the first two trimesters and a maximum of three times in the third trimester. Blood lead determinations were made by atomic absorption spectrophotometry. Potential sources or modifiers of lead exposure were collected by interviews, including sociodemographic, pregnancy history, occupational, and lifestyle data. Results confirmed a previously reported U-shaped curve in blood lead concentration during pregnancy as well as findings that blood lead levels increase with age, smoking, lower educational level, and African-American race and decrease with history of breastfeeding and higher intake of calcium. Additionally, interactions were found between time since last menstrual period and both maternal age and calcium. Specifically, older mothers showed steeper increases in blood lead concentrations during the latter half of pregnancy than did younger mothers, and intake of calcium had a protective effect only in the latter half of pregnancy, an effect that became stronger as pregnancy progressed. These findings provide further evidence that lead is mobilized from bone during the latter half of pregnancy and that calcium intake may prevent bone demineralization.

Adult↗
PubMed2000

Risk analysis for thoracoscopic lung volume reduction: a multi-institutional experience.

OBJECTIVE: Most reports of thoracoscopic lung volume reduction (TLVR) are relatively small and early experiences from a single institution, factors which limit both the statistical validity and the applicability to the population at large. In order to address these shortcomings we undertook an analysis of the TLVR experience at five separate institutions to assess operative morbidity and identify predictors of mortality. METHODS: Questionnaires were sent to four groups of surgical investigators at five institutions actively performing TLVR. Data was requested regarding preoperative, operative and postoperative parameters. Twenty-five potential predictors of mortality were analyzed and seven proved to be at least marginally significant (P<0.10). These parameters were entered into a stepwise logistic regression analysis to identify independent predictors. RESULTS: The 682 patients (415 males, 267 females, mean age 64.0 years) underwent unilateral (410) or bilateral (272) TLVRs. Overall, operative mortality was 6% with half of the deaths resulting from respiratory causes. The remaining patients were discharged to home (88%), a rehabilitation facility (4%) or a ventilator facility (2%). There were 25 perioperative factors chosen representing clinically important indices such as spirometry, oxygenation, functional status, clinical and demographic variables. Univariate analysis identified seven variables as predictors of mortality (P<0.10) and these were entered into a stepwise logistic regression analysis. Only age, 6-min walk, gender (male 8%, female 3% mortality) and the procedure performed (unilateral 4.6%, bilateral 8%) were independent predictors while preoperative steroid therapy, preoperative oxygen administration, and time since smoking cessation dropped out of the model. The specific institution, learning curve (early vs. late experience), type of lung disease, spirometric indices and predicted maximum VO(2) were not significant predictors. CONCLUSION: This experience suggests that unilateral and bilateral lung volume reduction procedure can be performed with acceptable morbidity and mortality. Although age, gender, exercise capacity and the procedure performed are all independent predictors of mortality, the risk of operative death did not appear excessive in this fragile patient subset.

Adult↗
PubMed1997

Thoracoscopic lung volume reduction surgery reduces dyspnea and improves exercise capacity in patients with emphysema.

Improved ventilation and exercise capacity follows thoracoscopic lung volume reduction surgery (TLVRS) in patients with severe emphysema. This improvement could be related to changes in inspiratory and expiratory flows following surgery, with consequent improvement in dyspnea indices. Changes in inspiratory/expiratory flows at rest and exercise and their relation to subjective improvement in dyspnea after TLVRS are not well known. We studied 25 patients with severe emphysema who underwent unilateral TLVRS performed in well-defined zones with decreased perfusion in nuclear medicine lung scans. Early follow-up after surgery (4.2 +/- 0.8 mo) showed significant improvements in exercise tolerance: The distance covered over a 6 min walk test increased from 934 +/- 297 to 1,071 +/- 241 ft (p = 0.01). Exercise tolerance using a bicycle ergometer showed increased exercise endurance from 4.43 +/- 1.7 to 5.71 +/- 1.8 min (p < 0.001). The maximum workload tolerated increased from 37 +/- 19 to 52 +/- 21 W (p < 0.01) and VO2 max changed from 9.7 +/- 2 to 11.8 +/- 3 (ml.kg)/min (p < 0.01). This increment was achieved by generating significantly larger minute ventilation (VE), from 24 +/- 11 to 29 +/- 10 L/min, reached through larger tidal volumes (increasing from 951 +/- 330 to 1,145 +/- 367 ml), while maintaining the same maximum respiratory rates. Increased VE was also accompanied by significant increases in both average inspiratory and expiratory flows measured during exercise: from 0.89 +/- 0.41 L/s to 1.06 +/- 0.08 L/s, and from 0.77 +/- 0.37 to 0.90 +/- 0.32 L/s respectively (p < 0.01). The parallel increment in flows resulted in constant T1/Ttot relationship. These functional changes correlated with increased inspiratory flows at rest measured with pulmonary function tests (forced inspiratory volume in one s [FIV1], expiratory flows [FVC, FEV1], and increased maximum voluntary ventilation [MVV]) following the surgically induced reduction in residual volume (RV). These objective changes occurred parallel to improved dyspnea indices. The Baseline Focal Score was 3.36 +/- 1.47 and the Transition Focal Score was 6.12 +/- 0.7. The objectively measured variables at rest that best correlated with subjective improvement in dyspnea were the change in MVV, change in resting arterial PaO2, and change in FEV1 following TLVRS. Exercise variables did not have significant correlation with subjective markers indicating improvement in dyspnea, with the exception of the change in Dyspneic Index [(VE/MVV)100] at maximum exercise.

Adult↗
PubMed1997

Histopathologic diagnosis made in lung tissue resected from patients with severe emphysema undergoing lung volume reduction surgery.

STUDY OBJECTIVES: This study reports histopathologic findings in a group of emphysema patients who underwent thoracoscopic lung volume reduction surgery (75) or sternotomy (five) with the purpose to induce functional improvement and relief of dyspnea. Immediate outcome and complications were correlated to histologic patterns. DESIGN: Histopathologic material obtained in lung volume reduction surgery in 80 consecutive patients was analyzed. Thirty patients who had other histopathologic diagnoses in addition to emphysema were grouped and compared with 50 patients found to have emphysema exclusively. Postoperative outcome and preoperative lung function variables were compared. MEASUREMENTS AND RESULTS: All patients had severe obstructive lung disease and significant air trapping preoperatively documented by pulmonary function testing. All had severe exertional dyspnea. All had chest radiographs, CT, and nuclear medicine lung scans consistent only with emphysema. All portions of resected lung tissue were weighed, lung volume was estimated, and routine histopathologic studies were made. Thirty patients (37.5%) had unsuspected findings such as interstitial fibrosis, noncaseating granulomatosis, chronic inflammation, and unsuspected neoplasia (three carcinomas, one carcinoid). Retrospective review of imaging studies in these patients failed to show infiltrative processes. The average lung weight resected in this group was significantly heavier (65+/-18 g) compared with the other group (56+/-13 g), although both had the same estimated lung volume. Average number of days requiring chest tubes and length of hospitalization was also significantly higher (12.8+/-19 vs 6.4+/-5 days with chest tubes and 17.4+/-22 vs 8.5+/-6 days of hospitalization, respectively). None of the preoperative pulmonary function tests variables were different between the two groups. Serious postoperative complications were more frequent in these patients compared with those who showed only emphysema. CONCLUSIONS: A significant portion of patients diagnosed as having severe emphysema will have other unsuspected histologic findings. When subjected to lung volume reduction surgery, this subgroup will have more serious complications and longer periods of air leaks, requiring longer hospitalization time. Retrospective review of imaging studies and preoperative pulmonary function tests used to select patients for lung volume reduction failed to identify this subgroup.

Adult↗
PubMed1997

Hemodynamics and gas exchange after single lung transplantation and unilateral thoracoscopic lung reduction.

BACKGROUND: Single lung transplantation and recently thoracoscopic lung reduction (TLR) have become surgical alternatives to manage emphysema. We report here early outcomes of 10 single lung transplant (SLT) recipients with severe emphysema compared with 10 patients treated with unilateral TLR. METHODS: Ten consecutive recipients of (SLT) and 10 patients undergoing unilateral TLR were studied. Both groups had measurements of preoperative pulmonary function and arterial blood gases. Hemodynamic measurements were made by use of a right ventricular ejection fraction/volumetric pulmonary artery catheter during and immediately after surgery in both groups to compare hemodynamic and gas exchange response in each procedure. Pulmonary function tests were repeated 3 months and 1 year after surgery. Complications and functional outcome are reported. RESULTS: Both groups had the same severity of obstructive disease (mean forced expiratory volume in 1 second = 20% +/- 5% for the SLT group and 23% +/- 9% for the TLR group) and similar patterns of right ventricular dysfunction. During operation, SLT recipients showed worse hypercapnia and pulmonary hypertension than TLR subjects when ventilation and perfusion to the operative lung were interrupted. Patients undergoing TLR only had interrupted ventilation, which was transiently reversed when severe hypoventilation or hypoxemia occurred. All patients undergoing TLR were extubated immediately after surgery. SLT recipients were extubated an average of 42 hours later. Pulmonary function testing performed 3 months after surgery showed improvement in both groups. SLT recipients showed larger improvements in airflow but comparable improvements in forced vital capacity. Both groups achieved similar improvements in gas exchange. This trend continued a year after surgery. Patients undergoing TLR were not subjected to complications of immunosuppressive therapy or exposed to opportunistic infections. CONCLUSIONS: Early results show TLR as an acceptable alternative to SLT in carefully selected patients with the same severity of obstructive lung disease. Long-term follow-up studies are needed to establish long-term differences in functional outcome and development of complications. TLR may be an option for patients with severe dyspnea related to emphysema who do not meet criteria for transplantation.

Aged↗
PubMed1997

Cisapride poisoning.

A MEDLINE search from 1966-1996 revealed no reports of cisapride poisoning. An 8-mo-old, 8.9 kg girl received 8 mL of cisapride (Propulsid Suspension, 1 mg/mL, Janssen Pharmaceutica, Titusville, NJ) rather than the usual dose of 0.8 mL, resulting in an inadvertent, 10-fold, iatrogenic, dosing error. She developed emesis, hyperactive bowel sounds, abnormal behavior, mild hyperthermia, tachycardia, hypertension, and thrombocytosis. This is the first published report of poisoning with cisapride.

Administration, Oral↗
PubMed1995

Neurobehavioral effects of low-level methanol vapor exposure in healthy human volunteers.

Methanol-powered vehicles are being introduced in the United States as a solution to air pollution. This study assessed whether acute exposure to methanol vapor at the current industrial threshold limit value of 200 ppm for 4 hr has adverse effects on human neurobehavioral performance. Twenty-six healthy subjects (15 men, 11 women; ages 26-51 years) were exposed to methanol or water vapor for 4 hr while seated in a chamber. The subjects served as their own controls in a randomized, double-blind study design. The variables assessed were serum and urine methanol and formate levels; visual performance (color discrimination and contrast sensitivity); and neurophysiological (auditory evoked potentials) and neurobehavioral performances. Exposure to methanol increased serum concentrations and urinary excretions of methanol, but did not affect formate levels. Overall visual, neurophysiological, and neurobehavioral test outcomes were not significantly affected, unless certain between-subject variables are considered. Slight effects on P-300 amplitude and Symbol Digit testing were noted. We conclude that acute exposure of healthy people to low concentrations of methanol had little effect on these measures of neurobehavioral performance.

Administration, Inhalation↗
PubMed1993

Diffusing capacity decreases after heart transplantation.

We evaluated the following spirometric values: forced vital capacity (FVC), first second expiratory volume (FEV1), FEV1/FVC, the lung volumes, total lung capacity (TLC), residual volume (RV), and single breath diffusing capacity for CO in 22 patients, before and after heart transplant. We found abnormal pulmonary function in 21 patients before heart transplantation. Despite postoperative increases in lung volumes in 10 patients, abnormal pulmonary function persisted in 20 patients after heart transplant. Mean values for lung volumes and flow rates did not change but diffusion for CO decreased significantly after heart transplantation. Diffusion failed to correlate with ejection fraction, pulmonary arterial pressure, pulmonary capillary wedge pressure (PCWP), and pulmonary vascular resistance; however, in a subset of patients with improved postoperative lung volumes, preoperative diffusion for CO correlated with preoperative PCWP. We conclude that pulmonary function abnormalities are common among heart transplant recipients. Diffusion abnormalities are not linearly related to indices of cardiac function measured before transplantation and diffusion abnormalities appear to be multifactorial in cause. The posttransplant decrease in diffusion appears to result from the combined effects of decreased postoperative lung volumes in some patients and relief of heart failure induced pulmonary vascular engorgement in others. Improvement in lung volumes and flow rates may occur but cannot be expected after heart transplantation, and diffusion decreases after heart transplantation. The fact that pulmonary function and lung volumes do not improve following heart transplantation implies to underlying lung disease or permanent lung alterations result from chronic heart failure.

Adult↗
PubMed1993

Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers.

The safety, efficacy and pharmacokinetic parameters of 5 g of hydroxocobalamin given intravenously, alone or in combination with 12.5 g of sodium thiosulfate, were evaluated in healthy adult men who were heavy smokers. Sodium thiosulfate caused nausea, vomiting, and localized burning, muscle cramping, or twitching at the infusion site. Hydroxocobalamin was associated with a transient reddish discoloration of the skin, mucous membranes, and urine, and when administered alone produced mean elevations of 13.6% in systolic and 25.9% in diastolic blood pressure, with a concomitant 16.3% decrease in heart rate. No other clinically significant adverse effects were noted. Hydroxocobalamin alone decreased whole blood cyanide levels by 59% and increased urinary cyanide excretion. Pharmacokinetic parameters of hydroxocobalamin were best defined in the group who received both antidotes: t1/2 (alpha), 0.52 h; t1/2 (beta), 2.83 h; Vd (beta), 0.24 L/kg; and mean peak serum concentration 753 mcg/mL (560 mumol/L) at 0-50 minutes after completion of infusion. Hydroxocobalamin is safe when administered in a 5 gram intravenous dose, and effectively decreases the low whole blood cyanide levels found in heavy smokers.

Adult↗
PubMed1990

Inhibition of palmitoyl co-enzyme A hydrolase in mitochondria and microsomes by pharmaceutical organic anions.

Rat microsomes and mitochondria were isolated and incubated with selected pharmaceutical organic anions at concentrations of 0, 0.2, 0.5, 1.0, and 2 mM. Activity of palmitoyl CoA hydrolase (PCAH) was shown to be reduced in a dose-dependent manner in microsomes by ibuprofen, valproate, acetyl salicylate, 2,4-dichlorophenoxyacetate (2,4-D), and 4-pentenoate, but not salicylate. Mitochondrial PCAH activity was inhibited by clofibrate, ibuprofen, valproate, and 2,4-D. Mitochondrial oxidative phosphorylation was impaired or uncoupled by each of the mitochondrial PCAH inhibitors. The inhibition of PCAH by some of these agents may lead to fatty acyl CoA accumulation. Very low concentrations of fatty acyl CoA are known to cause mitochondrial uncoupling and increase permeability. This action may play a role in the mitochondrial injury caused by some of these agents or related disease processes.

Animals↗
PubMed1990

Effects of 1,3-dichloropropene on the kidney of Fisher 344 rats after pretreatment with diethyl maleate, buthionine sulfoximine, and aminooxyacetic acid.

Acute nephrotoxicity of cis/trans-1,3-dichloropropene (DCP) was assessed in male Fisher 344 rats. Pretreatment of rats with corn oil, aminooxyacetic acid (AOA), buthionine sulfoximine (BSO), or diethyl maleate (DEM) was given intraperitoneally 1 h or 4 h prior to injection of DCP. Doses of DCP were 0, 25, 50, and 75 mg/kg intraperitoneally (4-5 animals per dose/pretreatment group). Urine was collected for 24 h. Excretion of creatinine, phosphorus, protein, N-acetylglucosaminidase (NAG), and the major metabolite of DCP, N-acetyl-S-(cis-3-chloroprop-2-enyl)-cysteine (3CNAC), was measured. Excretion of the metabolite, 3CNAC, increased in a dose-related manner from 0 to 50 mg/kg of DCP, but further increases were not seen at the 75 mg/kg dose. The pretreatments produced no alterations in the amounts of metabolite excreted when compared to corn oil controls. Zero-order metabolism or impaired metabolism is suggested to be occurring at high doses of DCP. The AOA pretreatment group showed no increase in the excretion of NAG, whereas other pretreatments (corn oil, BSO, DEM) showed elevations of NAG excretion at the highest DCP doses. AOA inhibits renal beta-lyase, an enzyme that mediates cleavage of mercapturic acid metabolites to toxic products. Since NAG excretion was not elevated in response to DCP with AOA pretreatment and was not raised by pretreatments that deplete glutathione, it is suggested that nephrotoxic effects of DCP may be mediated through the mercapturic acid metabolites on the kidney, rather than due to glutathione depletion per se.

Acetates↗
PubMed1988

Simultaneous ion-pair and partition liquid chromatography of acetaminophen, theophylline and salicylate with application to 500 toxicologic specimens.

Acetaminophen (A), salicylate (S), and theophylline (T) are three common pharmaceutical agents involved in drug overdose for which determinations of serum drug concentrations play a pivotal role in clinical management. All three must be included in overdose screening, but often separate methods must be used. By combining reverse phase high performance liquid chromatography (HPLC) for A and T with ion-pair techniques for S, all three drugs can be chromatographed and quantitated simultaneously. A water-soluble ion-pair of S and 2-amino-2-(hydroxy-methyl)-1,3-propanediol eluted in a mobile phase of 4% acetonitrile and 12% acetic acid in water. Relative retention times for A, T and S were 0.41, 0.57 and 1.75 with an internal standard of 8-chlorotheophylline. Validation studies demonstrated recoveries of 88-104%, intraasay precisions of 2.1-6.6%, interassay precision of 3.8-8.0%, detection limits and linearity ranges of 2-200 mg/l for A and T and 10-1,000 for S. Seventy-two drugs were tested for interference. Accuracy studies showed no significant biases when compared to other methods. The method is convenient for toxicologic screening or therapeutic drug monitoring. In 576 consecutive serum specimens submitted for general toxicologic screening, 7.3% were positive for A, 5.2% for S, and 1.7% for T. Only 1.7% had critical concentrations indicating intoxication.

Acetaminophen↗
PubMed1988

Blood pressure and blood lead concentration in bus drivers.

San Francisco bus drivers have an increased prevalence of hypertension. This study examined relationships between blood lead concentration and blood pressure in 342 drivers. The analysis reported in this study was limited to subjects not on treatment for hypertension (n = 288). Systolic and diastolic pressures varied from 102 to 173 mm Hg and from 61 to 105 mm Hg, respectively. The blood lead concentration varied from 2 to 15 micrograms/dL. The relationship between blood pressure and the logarithm of blood lead concentration was examined using multiple regression analysis. Covariates included age, body mass index, sex, race, and caffeine intake. The largest regression coefficient relating systolic blood pressure and blood lead concentration was 1.8 mm Hg/ln (micrograms/dL) [90% C. I., -1.6, 5.3]. The coefficient for diastolic blood pressure was 2.5 mm Hg/ln (micrograms/dL) [90% C. I., 0.1, 4.9]. These findings suggest effects of lead exposure at lower blood lead concentrations than those concentrations that have previously been linked with increases in blood pressure.

Adult↗